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bioRxiv · 10.1101/2024.02.03.578580

IFNγ induces epithelial reprogramming driving CXCL11-mediated T cell migration

Cutilli, A.·Jansen, S. A.·Paolucci, F.·Mokry, M.·Mocholi, E.·Lindemans, C. A.·Coffer, P. J.
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Abstract

The cytokine interferon-gamma (IFN{gamma}) plays a multifaceted role in intestinal immune responses ranging from anti-to pro-inflammatory depending on the setting. Here, using a 3D co-culture system based on human intestinal epithelial organoids, we explore the capacity of IFN{gamma}-exposure to reprogram intestinal epithelia and thereby directly modulate lymphocyte responses. IFN{gamma} treatment of organoids led to transcriptional reprogramming, marked by a switch to a pro-inflammatory gene expression profile, including transcriptional upregulation of the chemokines CXCL9, CXCL10, and CXCL11. Proteomic analysis of organoid-conditioned medium post-treatment confirmed chemokine secretion. Furthermore, IFN{gamma}-treatment of organoids led to enhanced T cell migration in a CXCL11-dependent manner without affecting T cell activation status. Taken together, our results suggest a specific role for CXCL11 in T cell recruitment that can be targeted to prevent T cell trafficking to the inflamed intestine.

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Cutilli, A., Jansen, S. A., Paolucci, F., Mokry, M., Mocholi, E., Lindemans, C. A., Coffer, P. J.. 2024-02-07. IFNγ induces epithelial reprogramming driving CXCL11-mediated T cell migration. https://doi.org/10.1101/2024.02.03.578580

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